ABSTRACT ? CANCER MECHANISMS (CM) RESEARCH PROGRAM Program Leaders: Ramon Parsons, MD, PhD and Ross Cagan, PhD The main goal of the Cancer Mechanisms (CM) Program of the Tisch Cancer Institute (TCI) is to facilitate basic research that is pertinent to improving the diagnosis, treatment and prevention of cancer. The premise of our program is that basic research on genetic, biochemical, and developmental pathways that drive cancer initiation and progression will reveal novel therapeutic targets for cancer. We recognize that effective identification and characterization of therapeutic targets must be grounded in detailed studies of human disease. CM investigators study important aspects of cancer development, perform gene discovery research in model organisms ranging from fission yeast to human cells and tissues, and explore mechanisms of cancer cell sensitivity and resistance to targeted therapy. Others design and implement clinical trials for cancer therapeutics developed at the Icahn School of Medicine at Mount Sinai (ISMMS). All of these approaches contribute to our overall goal of translating basic research advances to the clinical setting. The membership is organized around three scientific themes focused around signaling networks, epithelial cancer, and chromatin regulation/repair to accomplish our overarching specific aims: 1. To elucidate critical pathways that drive cancer development. 2. To identify candidate therapeutics that effectively target these pathways. 3. To foster intra- and inter-program collaborations that accelerate novel target and therapy development. 4. Train an outstanding cadre of graduate students, and postdoctoral and clinical fellows in cancer biology. The CM program has 49 members: 41 full members and 8 associate members. They represent 13 departments and 5 institutes (the TCI, Black Family Stem Cell Institute, Diabetes, Obesity and Metabolism Institute, Experimental Therapeutics Institute, and the Icahn Institute for Genomics and Multiscale Biology). As of July 1, 2014, program members were awarded $18,307,892 in NCI and other peer-reviewed cancer-related direct support. Members of the CM Program have been increasingly successful in publishing their research in high impact journals. Since 2011, CM program members published 346 reports, of which 14.2% were intra-programmatic and 11.6% inter-programmatic.